Differential VASP phosphorylation controls remodeling of the actin cytoskeleton

Benz, P.; Blume, Constanze; Seifert, Stefanie; Wilhelm, Sabine; Waschke, Jens; Schuh, Kai; Gertler, Frank B.; Münzel, Thomas; Renné, Thomas

doi:10.1242/jcs.044537

Cited by 155 publications

(248 citation statements)

References 69 publications

(128 reference statements)

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“…On the other hand, VASP binding to focal adhesion protein and profilin, a regulator of actin polymerization, are independent of the VASP phosphorylation status [48,51]. Additionally, the phosphorylation at Ser157 of VASP influenced VASP localization, but little impact on F-actin assembly [14]. In our experiment, inhibition of PKC-mediated VASP phosphorylation resulted in suppression of local actin aggregation, which indicate that the phosphorylation of VASP is required for UDPinduced actin aggregation.…”

Section: Udp-induced Vasp Phosphorylation At Ser157 Is Mediated By Rhmentioning

confidence: 45%

“…Molecular functions of VASP are regulated by several phosphorylation sites [14,15]. We found that UDP induced the transient phosphorylation of VASP at Ser157.…”

Section: Udp Induced the Phosphorylation And Translocation Of Vaspmentioning

confidence: 81%

“…VASP is known to be regulated by phosphorylation [14]. Three phosphorylation sites are identified: Ser157 is phosphorylated by PKA, Ser239 is phosphorylated by PKG [26] and Thr278 is a less favored site for both PKA and PKG and reported to be phosphorylated by AMPactivated kinase [27].…”

Section: Udp-induced Vasp Phosphorylation At Ser157 Is Mediated By Pkcmentioning

confidence: 99%

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Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Kataoka¹,

Koga²,

Uesugi³

et al. 2011

Purinergic Signalling

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Microglia are major immunocompetent cells in the central nervous system and retain highly dynamic motility. The processes which allow these cells to move, such as chemotaxis and phagocytosis, are considered part of their functions and are closely related to purinergic signaling. Previously, we reported that the activation of the P2Y 6 receptor by UDP stimulation in microglia evoked dynamic cell motility which enhanced their phagocytic capacity, as reported by Koizumi et al. (Nature 446 (7139):1091-1095. These responses require actin cytoskeletal rearrangement, which is seen after UDP stimulation. However, the intracellular signaling pathway has not been defined. In this study, we found that UDP in rat primary microglia rapidly induced the transient phosphorylation at Ser157 of vasodilator-stimulated phosphoprotein (VASP). VASP, one of actin binding protein, accumulated at the plasma membrane where filamentous (F)-actin aggregated in a time-dependent manner. The phosphorylation of VASP was suppressed by inhibition of PKC. UDP-induced local actin aggregations were also abrogated by PKC inhibitors. The Rho inhibitor CT04 and the expression of p115-RGS, which suppresses G 12/13 signaling, attenuated UDP-induced phosphorylation of VASP and actin aggregation. These results indicate that PKC-and Rho-dependent phosphorylation of VASP is involved in UDP-induced actin aggregation of microglia.

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Section: Udp-induced Vasp Phosphorylation At Ser157 Is Mediated By Rhmentioning

confidence: 45%

“…Molecular functions of VASP are regulated by several phosphorylation sites [14,15]. We found that UDP induced the transient phosphorylation of VASP at Ser157.…”

Section: Udp Induced the Phosphorylation And Translocation Of Vaspmentioning

confidence: 81%

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Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Kataoka¹,

Koga²,

Uesugi³

et al. 2011

Purinergic Signalling

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“…DII-Spectrin, via its SH3 domain, has been also implicated in initiating Rac activation in the specialized E3 integrin clusters that initiate cell adhesion and spreading [35]. Moreover, the SH3 domain of DII-spectrin was demonstrated to bind proteins involved in the regulation of actin cytoskeleton dynamics such as two members of the Mena-VASP family (EVL, VASP) and Tes [36][37][38][39]. VASP participates in actin fiber formation and the DII-spectrin-VASP complexes regulate cortical actin cytoskeleton assembly with implications in cell-cell contact formation.…”

Section: Consequences On Actin Dynamicsmentioning

confidence: 99%

Novel role for the Lu/BCAM–spectrin interaction in actin cytoskeleton reorganization

Collec

Lecomte

Nemer

et al. 2011

Biochemical Journal

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SynopsisLu/BCAM is a laminin 511/521 receptor, expressed in erythroid and endothelial cells, and in epithelial tissues. The RK573-574 motif of Lu/BCAM cytoplasmic domain interacts with DI-spectrin, the main component of the membrane skeleton in red blood cells. We report that Lu/BCAM binds to the non-erythroid DII-spectrin via the RK573-574 motif. Alanine substitution of this motif abolished the Lu/BCAM-spectrin interaction, enhanced Lu/BCAM half-life at the MDCK cell surface and increased Lu/BCAM-mediated cell adhesion and spreading on laminin 511/521. We showed that the Lu/BCAM-spectrin interaction mediated actin reorganization during cell adhesion and spreading on laminin 511/521. This interaction was involved in a laminin 511/521 to actin signaling pathway leading to stress fibers formation. This skeleton rearrangement was associated with an activation of the small GTP binding protein RhoA, which depended on the integrity of the Lu/BCAM laminin 511/521 binding site. It also required the Lu/BCAM-DII-spectrin interaction since its disruption decreased stress fibers formation and RhoA activation. We conclude that the Lu/BCAM-spectrin interaction is required for stress fibers formation during cell spreading on laminin 511/521 and that spectrin acts as a signal relay between laminin 511/521 and actin that is involved in actin dynamics.

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“…S1), is the only phosphorylation site conserved amongst VASP, Mena and EVL. Phosphorylation at Ser153 is associated with increased VASP localization to focal adhesion-like structures and the plasma membrane (Benz et al, 2009;Döppler et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery

2015

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Shigella spp. are intracellular bacterial pathogens that cause diarrhoeal disease in humans. Shigella utilize the host actin cytoskeleton to enter cells, move through the cytoplasm of cells and pass into adjacent cells. Ena/VASP family proteins are highly conserved proteins that participate in actin-dependent dynamic cellular processes. We tested whether Ena/VASP family members VASP (vasodilator-stimulated phosphoprotein), Mena (mammalian-enabled) or EVL (Ena-VASP-like) contribute to Shigella flexneri spread through cell monolayers. VASP and EVL restricted cell-to-cell spread without significantly altering actin-based motility, whereas Mena had no effect on these processes. Phosphorylation of VASP on Ser153, Ser235 and Thr274 regulated its subcellular distribution and function. VASP derivatives that lack the Ena/VASP homology 1 (EVH1) domain or contain a phosphoablative mutation of Ser153 were defective in restricting S. flexneri spread, indicating that the EVH1 domain and phosphorylation on Ser153 are required for this process. The EVH1 domain and Ser153 of VASP were required for VASP localization to focal adhesions, and localization of VASP to focal adhesions and/or the leading edge was required for restriction of spread. The contribution of the EVH1 domain was from both the donor and the recipient cell, whereas the contribution of Ser153 phosphorylation was only from the donor cell. Thus, unlike host proteins characterized in Shigella pathogenesis that promote bacterial spread, VASP and EVL function to limit it. The ability of VASP and EVL to limit spread highlights the critical role of focal adhesion complexes and/or the leading edge in bacterial passage between cells.

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Differential VASP phosphorylation controls remodeling of the actin cytoskeleton

Cited by 155 publications

References 69 publications

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Novel role for the Lu/BCAM–spectrin interaction in actin cytoskeleton reorganization

Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery

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